Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II

J Mol Biol. 2017 Oct 27;429(21):3146-3155. doi: 10.1016/j.jmb.2016.11.006. Epub 2016 Nov 13.


The faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The stalling of RNAP2 on a transcription-blocking lesion triggers a series of highly regulated events, including RNAP2 processing to make the lesion accessible for DNA repair, R-loop-mediated DNA damage signaling, and the initiation of transcription-coupled DNA repair. The correct execution and coordination of these processes is vital for resuming transcription following the successful repair of transcription-blocking lesions. Here, we outline recent insights into the molecular consequences of RNAP2 stalling on transcription-blocking DNA lesions and how these lesions are resolved to restore mRNA synthesis.

Keywords: DNA damage; RNA polymerase 2; nucleotide excision repair; transcription coupled repair; transcription restart.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Damage*
  • DNA Repair / physiology*
  • Humans
  • RNA Polymerase II / metabolism*
  • Signal Transduction
  • Transcription, Genetic*


  • RNA Polymerase II